PROJECT SUMMARY/ABSTRACT Dr. Alka Kanaya is Professor in the Departments of Medicine, Epidemiology and Biostatistics at the University of California San Francisco. Trained in Internal Medicine and Epidemiology, over the past decade she has mentored several individuals at different levels in their training and developed a thriving program of multidisciplinary collaborative research focused on cardiovascular disease epidemiology and prevention. She is currently funded by the NHLBI to conduct a prospective cohort study of South Asians called the MASALA study which is modeled on the existing Multi-Ethnic Study of Atherosclerosis (MESA) to understand the antecedents of cardiovascular disease in this high risk ethnic group. With the support of the K24 renewal, Dr. Kanaya will extend the research program by adding measures of coronary artery cross-sectional area to further knowledge on atherosclerosis markers and ASCVD. The Overall Aims of this K24 proposal are: (1) To measure coronary artery size (cross-sectional area and diameter) among 500 South Asians (age 45-65 years) in the MASALA study and describe coronary artery size by age, sex, and CAC category. (2) To compare coronary size of similar aged South Asians in MASALA with Whites and African Americans in CARDIA after adjusting for age, sex, body mass index and cardiovascular risk factors. (3) To determine the association between coronary artery size in South Asians with known cardiovascular risk factors, ectopic fat distribution, and biomarkers. (4) To determine whether previously discovered genetic variants and local methylation patterns for cardiometabolic traits generalize to South Asians, and then to investigate the association between common genetic variants and DNA methylation patterns with coronary artery size. The K24 would insure sufficient time to pursue this next phase in Dr. Kanaya's research while protecting time to devote to mentoring future clinical investigators in patient-oriented research. The plans for development, research, and mentoring were designed to complement each other and to create a synergistic effect of mentoring and research in patient-oriented research. The proposed mentoring, research, and career development activities actively leverage existing infrastructure, resources, and training initiatives provided by NIH including the CTSI, and Dr. Kanaya's active research program at UCSF.